The MGH Interdepartmental Stroke Center Grant will continue its efforts to characterize changes in brain physiology prior to and following stroke in order to develop better treatment modalities. Dr. Ames will use an in vitro preparation to identify the earliest cellular changes in CNS ischemia; he will assay for toxic intermediates released by ischemic insults, and he will examine the effectiveness of various anesthetics, transmitter blockers, and membrane "tightners" in protecting against ischemic damage. Dr. Ackerman and colleagues will use positron emission tomography (PET) in stroke-prone patients to explore the effects of vascular lesions on cerebral blood flow (CBF) and oxygen metabolism (CMRO2), in order to identify patients with low flow states at risk for ischemic events. In acute stroke patients they will study changes in CBF and CMRO2 that distinguish viable and nonviable tissue and they will examine the effects of treatment, such as hemodilution, on regional physiology and tissue outcome. Dr. Alpert will continue the validation studies, initially in an animal model, of brain pH measurements using PET imaging of the distribution of 11CO2; documenting acute changes in pH can help characterize treatable alterations in acute brain ischemia. Dr.\Correia will continue to coordinate the PET Labortory Core facilities for these PET projects. Dr. Kistler and colleagues will examine proton magnetic resonance (MR) images for signal changes that correlate with PET findings which distinguish viable and nonviable tissue, so that a more widely disseminated methodology might be used for documenting such tissue changes in the future.